Faster and Better Word Learning in Normal Humans: Transmission of Nerve Impulses - Essay Example

Levopoda: Faster and Better Word Learning in Normal Humans Aim of the research paper: To test the hypothesis that increasing brain dopamine levels by oral administration of its precursor L-dopa will improve the acquisition of cognitive skills during massed training even in normal humans. Findings: 1. L-dopa in normal humans can accelerate word learning 2. Markedly increase overall success 3. Capable of accelerating gain of function during skill acquisition or reacquisition. 4. L-dopa is also given to patients with neurological disorder (Parkinson’s Disease) and for healthy individuals, receiving an acetyl cholinesterase inhibitor or amphetamine help improves learning. 5. Hedonic effect of dopamine Transmission of Nerve impulses Neurons in the cells from the nervous system send and receive messages to and from each other in the body. They perform this function through a two-part process called neural signalling. It begins with the generation of an electrical impulse that is passed down the length of one neuron. An electrical impulse is generated when a stimulus such as sensory input causes a rapid change in electrical charge in one part of a neuron’s membrane. This electrical impulse is one unit of neural information. An electrical impulse flowing along the length of a neuron is called nerve impulse. Nerve impulses are unidirectional within a neuron – from the dendrite through the cell body and axon, to the axon terminals. In addition, neurons produce nerve impulses in an all-or-nothing way. For example, if the stimulus that a neuron receives is too weak to trigger a nerve impulse, nothing happens – the neuron does not initiate an impulse. However, if the stimulus is strong enough, the neuron does initiate an impulse. Transmission of nerve impulses: chemical transmission What happens when an impulse reaches the end of one neuron and move to another neuron? The junction between two neurons or between a neuron and a muscle is called a synapse. The two cells involved in a synapse do not physically touch each other instead they are separated by a small space. The cell that carries the impulse to the synapse is the synaptic cell and the cell that receives the impulse is the postsynaptic cell. When an impulse that is travelling along the postsynaptic cell reaches the end of the axon, it causes the cell to release molecules known as neurotransmitters. These molecules are released into the synapse and diffuse approximately 20 millionths of a millimetre to where they bind with receptors on the dendrites of the postsynaptic cell. When neurotransmitters bind to the receptors, the charge across the postsynaptic membrane changes and if the change is great enough, it triggers a nerve impulse, the nerve impulse then travels along the postsynaptic cell. Chemistry of Dopamine: Dopamine (DA) is a predominant catecholamine neurotransmitter in the mammalian brain where it controls a variety of functions including locomotor activity, cognition, emotion, positive reinforcement, etc. The chemical is naturally produced in the body (brain region). Dopamine, the neurotransmitter activates dopamine receptors. In addition, dopamine also works as a neurohormone, which is released by the hypothalamus. The main function of the neurohormone is to inhibit the release of prolactin from the anterior lobe of the pituitary. Dopamine can be externally supplied as a medication that acts on the sympathetic nervous system and produces effects such as increased heart rate and blood pressure. In natural forms, dopamine cannot cross the blood-brain barrier and dopamine given, as a drug through external sources does not directly affect the central nervous system (CNS). However, to increase the amount of dopamine in the brain region for patients suffering from Parkinson’s Disease, a synthetic precursor such as L-dopa (Levodopa) is given along with carbidopa, as they are capable of crossing the blood-brain barrier. Dopamine is directly associated with the reward system. Commonly associated with the pleasure system of the brain, dopamine also provides feelings of enjoyment and reinforcement and motivates persons to proactively perform certain activities. However, dopamine pathways are pathologically altered in addicted person. Cocaine works as a dopamine transporter blocker and inhibits dopamine uptake to increase the lifetime of dopamine. Amphetamine, like cocaine also increases the concentration of dopamine in the synaptic gap using a different mechanism. The dopaminergic systems have been the focus of much research over the past 30 years mainly because several pathological conditions such as Parkinson’s Disease, Schizophrenia, Tourette’s syndrome and hyperprolactinemia have been linked to a dysregulation of dopaminergic transmission. Dopamine Agonists and their effect on Parkinson’s Disease Parkinson’s Disease: It is a neural disorder that affects nerve cells or neurons in the brain that controls muscle movement. Due to the inactive nature or the absence of neurotransmitter, dopamine, signals are not coordinated and muscle movements are directly hampered. The symptoms of Parkinson’s Disease may include: trembling of hands, arms, stiffness of the arms, slowness of movement, and poor balance and coordination, etc. Drug Therapy for Parkinson’s Disease: The aim of the drug treatment is to increase the level of dopamine in the brain so that it could transmit signals to the muscle cells for normal functioning. Levodopa or L-dopa is the first line medicine for the disease. It is the dopamine precursor that is used in the manufacturing of dopamine. Brain cells can use this precursor to manufacture dopamine. The external dose of Levodopa helps normalize motor symptoms and make the muscle mobile and flexible. In addition, there are various dopamine agonists available such as Bromocriptine, rapinirole, pramipexole, etc, which are widely used agonists being used for the treatment of PD. The dopamine agonist drugs stimulate D2 receptor, most important for the motor symptoms of PD. In addition, these drugs also stimulate D3 receptor, which is involved in mood, personality, emotion as well as motor symptoms. Chemistry of Levodopa Levodopa or L-dopa is an intermediate in dopamine biosynthesis. Clinically, L-dopa is used in the treatment and management of Parkinson’s Disease. Levopoda is used as a prodrug to increase dopamine levels for the treatment of Parkinson’s Disease, since it is able to cross the blood brain barrier whereas dopamine itself cannot. Once L-dopa enters the CNS (Central Nervous System), it is motabolized to dopamine by aromatic L-amino acid decarboxylase. However, conversion to dopamine also occurs in the peripheral tissues, causing adverse effects and decreasing the available dopamine to CNS so it is a standard practice to coadminister a peripheral DOPA decarboxylase inhibitor. Mode of action of Levodopa L-dopa is rapidly absorbed from the small intestine by an active transport system for aromatic amino acids. The rate of absorption of Levopoda is greatly dependent upon the rate of gastric emptying; the pH of gastric juice and the length of time the drug is exposed to the degradative enzymes of the gastric mucosa and intestinal flora. However, since L-dopa is taken in combination with carbidopa, a drug, which prevents levodopa from being metabolised in the gut, liver and other tisseues, thus allowing more levodopa to reach the brain and allowing for a reduced dosage, thus reducing some of the side effects. In healthy humans, L-dopa is mostly taken up and converted by dopaminergic fibers and then can be physically released into the synaptic cleft. Toxic effects of Levodopa with or without Carbidopa are considerable: Physical side effects: Low Blood Pressure: This is a common problem during the first few weeks, particularly if the initial dose is too high. However, the addition of extra supplements of carbidopa reduces this effect to some degree. Arrhythmia: The drug may cause abnormal heart rhythms. Person suffering from arrhythmia may have symptoms such as fast or slow heart beat, skipping beats, chest pain or shortness of breath, etc. Gastrointestinal effects: Stomach and intestinal side effects are common even with carbidopa. Taking the drug with food can alleviate nausea. Effects in the Lung: Levopoda can cause disturbances in breathing function Psychiatric and Mental Side Effects: Confusion Extreme emotional states, particularly anxiety Visual and possibly auditory hallucinations Effects on learning: L-dopa appears to have mixed effects on learning functions would seem to work against any sort of enhanced memory. Dopamine system of the brain is generally divided into three components: 1. Mesostriatal (also called nigrostriatal) 2. Mesolimbic 3. Mesocortical Dopamine neurons exist in several parts of the brain, however, the research paper we are interested in form two dopaminergic pathways: long, thin bundles of cells, which connect areas of the midbrain to areas in the forebrain. The mesostriatal pathway links the substantia nigra in the midbrain to the striatum in the forebrain. The mesolimbic pathway connects the ventral tegmental area in the midbrain to the amygdala, the nucleus accumbens and the medial prefrontal cortex, again located in the forebrain. And the mesocortical dopamine fibers predominantly arise from the ventral tegmental area. Though the mesostriatal dopaminergic system is vital for the modulation of the motor system, dopaminergic neurons from the ventral tegmental area have a prominent role in associative learning by modulating signal processing. Specificity of learning is established by dopaminergic coactivation of target neurons involved in the processing of a particular behaviour. More sustained release of dopamine occurs during prolonged periods of uncertainty about payoffs and may promote learning by allocating attention to predictors for reward. Dopamine action on receptors There are at least 5 different receptor subtypes: D1, D2, D3, D4, D5. These receptors have been classified into two groups on the basis of their ability to stimulate or inhibit the enzyme adenylate cyclase. D1-like receptor family includes D1 and D5 subtypes: The Gs protein is involved and adenylyl cyclase would be activated. The action of the enzyme causes the conversion of adenosine triphosphate to cyclic monophosphate (cAMP). D2-like receptor family includes D2, D3, and D4 subtypes: The receptor combines with Gi protein and its activated alpha subunit then inhibits adenylyl cyclase so that the concentration of the cAMP is reduced. It is to be noted that for humans, there is no selective D1-like agonists available. The dopamine agonist bromocriptine, which is often prescribed for Parkinson’s Disease is selective for D2-like receptors. From the present study, we cannot say that learning enhancement by L-dopa is attributable to activation of one rather than the other receptor subtype or a combination of receptors. Issues associated with the findings The experiment done on healthy humans for the prediction of learning enhancement-using L-dopa clearly indicates that the dose of L-dopa plays a significant role in the training process. In addition, it is unclear, which receptor class is more involved in the learning process. Future research in this area is inevitable. From the study, it has been found that Levodopa or L-dopa plays a significant role in learning enhancement. However, cognitive enhancement is possible in healthy humans, other significant legal, regulatory and ethical questions arise. Though L-dopa is medically prescribed for people suffering from Parkinson’s Disease – it is sometimes taken chronically. Hedonic effects of drugs are mediated by their action on dopamine systems. The repeated administration of drugs (L-Dopa) can produce persistent neuroadaptations in the normal system responsive for incentive salience attribution, adaptations that render these systems hypersensitive (sensitised). Sensitisation leads to pathological wanting that can be dissociated from the hedonic effects of drugs. Other area of research comprising the effect of L-dopa and dopamine agonists may help clarify the role of phasic dopamine release on the overall success of learning. Gambling among Parkinson’s Disease patients: raising questions about dopamine effect on brain (Schnabel). Many people with Parkinson’s disease have been found to experience dramatic personality change and become more impulsive, and addiction prone pleasure-seekers. With high rate of pathological outcomes seen among patients, researchers need to rethink about how neurotransmitter dopamine works in diseased and normal brains. Parkinson’s medications do seem to restore dopamine levels to near normal in brain regions more affected by the disease such as the dorsal striatum. However, these medications also may drive dopamine levels above normal in other, less disease-affected centers such as the ventral striatum – one of the hotspots of the reward system. Work Cited S, Knecht. "Levodopa: faster and better word learning in normal humans." PubMed (2004): 7. Web. 3 Dec 2009. . Schnabel, Jim. "Gambling among Parkinson’s Patients Raises Questions about Dopamine." DANA Foundation 21-9-2009: n. pag. Web. 4 Dec 2009. . Read More